1. Field of the Invention
The present invention relates to specific lasers to be used in laser assisted tissue welding (LTW) and novel solders to be used in conjunction therewith that impart enhanced torque and tensile strength to tissue that has been sutured or sealed using LTW.
2. Description of the Related Art
In the past, damaged tissue was repaired using a variety of conventional sutures such as stitches or staples. More recently, the use of radiation, such as lasers, has been utilized to suture or weld tissue and seal leaks. Laser assisted tissue welding (LTW) can be achieved by directing a low energy laser beam of appropriate wavelength at the edges or surface of a tissue cut. The technique has gained the interest of the medical profession as an attractive new tissue repair procedure. In the LTW procedure, the wounded tissue is illuminated by radiation that directly or indirectly heats the tissue constituents, causing bonding to occur in the tissue structure and linking previously unattached tissues. Repair of damaged tissue can thus be achieved in greatly reduced time compared to that required by conventional suture techniques. Other advantages that this type of laser surgery has over traditional suture techniques have been reported, such as less foreign body reaction, less constriction, and reduced surgical time. While the LTW technique has found success in the experimental and clinical arenas, a wider usage is envisioned with further improvements in the procedure. In principle the LTW operation may be utilized wherever a tissue injury is present in an animal, including humans. However, it is especially suited to wounds to the skin, veins, arteries, respiratory tract, digestive tract, stomach, bladder and cervix.
Several investigators have worked on laser closure of wounds (White et al., Comparison of Laser Welded and Sutured Aortotomies, Arch Surg, 1986, 121:1133–1135 (1986); White, J. V., Laser Tissue Repair with the CO2 Laser, Poc SPIE, 1086 (1989); Oz et al., In Vitro Comparison of THC:YAG and Argon Ion Lasers for Welding of Biliary Tissue, Lasers Surg Med 9:248–253 (1989); White et al., Argon Laser Welded Arteriovenous Anastomoses, J Vasc Surg; 6:447–453 (1987)). Early contributions concentrated on welding tissues using lasers of different wavelengths applied directly to wound edges. Investigating the microstructural basis of the tissue fusion thus produced, Schober and coworkers proposed that there occurred a “homogenizing change in collagen with interdigitation of altered individual fibrils” (Schober et al., Laser Induced Alteration of Collagen Substructure Allows Microsurgical Tissue Welding, Science 232:1421–2, (1986)). These investigators, as well as others, proposed that the concentrated heating of the collagen fibrils above a threshold level allowed for their cross-linking (Goosey et al., Crosslinking of Lens Crystallins in a Photodynamic System: a Process Mediated by Singlet Oxygen, Science, 208:1278–1280 (1980); Chacon et al., Singlet Oxygen Yields and Radical Contributions in the Dye-sensitised Photo-oxidation in Methanol of Esters of Polyunsaturated Fatty Acids (Oleic, Linoleic, Linoleic and Arachidonic), Photochem Photobiol, 47:647–656, (1988); Tanzer, M. L., Cross-linking of Collagen, Science, 180:561–6 (1973)). Unfortunately, the heat necessary to allow this reaction to occur causes collateral thermal damage. Even a slight distortion, in ocular tissue for example, may have functional consequences. Also, the event of laser weld failure, the edges of the tissues may be damaged by the original treatment and cannot be re-exposed to laser energy (Oz, et al., Tissue Soldering by Use of Indocyanine Green Dye-enhanced Fibrinogen with the Near Infrared Diode Laser, J Vasc Surg, 11:718–25 (1990)). As used herein, “solder” is a biological glue based on proteins and other compounds that can provide greater bond strength, lesser collateral damage, and a bigger parameter window for achieving a successful bond. Bass L S and Treat M R; Laser Tissue Welding: A Comprehensive Review of Current and Future Clinical Applications: Lasers in Surgery and Medicine, 17:315–349 (1995).
Further work attempted to enhance heat-activated cross-linking by placing a dye in the wound. It was reported that matching the absorbance of the dye with the laser wavelength allowed an adhesive effect to be achieved with less laser power output and collateral thermal injury (Chuck et al., Dye-enhanced Laser Tissue Welding, Lasers Surg Med, 9:471–477 (1989); Foote C S, In Free Radicals in Biology, W A Pryor, Ed. Vol 2, p. 85, Academic Press, New York, (1976); Oz et al., Indocyanine Green Dye-enhanced Welding with a Diode Laser, Surg Forum, 40:316–8 (1989)). Coupling the dye with a protein to create a tissue “solder” was also investigated. The protein of choice has been fibrinogen, and in particular autologous fibrinogen in order to avoid problems of the transfer of viral diseases through the use of blood components from pool donors. In previous applications, fibrinogen was obtained as a fraction of whole blood. It is not pure fibrinogen, but also contains other blood elements, such as clotting factors. Application of such a protein-dye mixture in various animal models proved to be an improvement to dye alone (Oz, et al., Tissue Soldering by Use of Indocyanine Green Dye-enhanced Fibrinogen with the Near Infrared Diode Laser, J Vasc Surg, 11:718–25 (1990); Moazami et al., Reinforcement of Colonic Anastomoses with a Laser and Dye-Enhanced Fibrinogen, Arch Surg, 125:1452–1454 (1990)). Unfortunately, human application was forestalled owing to the need to isolate the needed protein (fibrinogen) from the patient prior to the procedure to avoid the risks of contamination and infection from donor plasma.
Comparisons of protein-dye versus sutured closures have found the protein-dye group to produce less of an inflammatory response, result in greater collagen production, greater mean peak stress at rupture and better cosmesis (Wider et al., Skin Closure with Dye-Enhanced Laser Welding and Fibrinogen, Plastic Reconstr Surg, 88:1018–1025 (1991)).
Although several tissue adhesives have been formulated, few have seen widespread use clinically. Laser-activated tissue glues have been used in skin closures as well as vascular and bowel anastomoses (Chuck et al., Dye-enhanced Laser Tissue Welding, Lasers Surg Med, 9:471–477 (1989); Moazami et al., Reinforcement of Colonic Anastomoses with a Laser and Dye-Enhanced Fibrinogen, Arch Surg, 125:1452–1454 (1990); Wider et al., Skin Closure with Dye-Enhanced Laser Welding and Fibrinogen, Plastic Reconstr Surg, 88:1018–1025 (1991); Auteri et al., Laser Activation of Tissue Sealant in Hand-Sewn Canine Esophageal Closure, J Thor Card Surg, 103:781–783, (1992)). One of the more successful products thus far has been a mixture of cryoprecipitated fibrinogen and a dye that absorbs laser energy and releases it in the form of heat at the wound interface (Moazami et al., Reinforcement of Colonic Anastomoses with a Laser and Dye-Enhanced Fibrinogen, Arch Surg, 125:1452–1454 (1990); Oz et al., Tissue Soldering by Use of Indocyanine Green Dye-enhanced Fibrinogen with the Near Infrared Diode Laser, J Vasc Surg, 11:718–25 (1990)).
Several key areas have been identified in which improvements must be made before LTW becomes widely used for tissue repair. First, the bursting strengths of blood vessel anastomoses repaired by LTW must be improved since past bursting strengths have been found to be less than that using conventional suture repair. Secondly, unwanted aneurysm formation has been recorded in the range of 6–29% with traditional LTW. The tensile strength of existing protein solders themselves is insufficient to explain the recorded improvements and the role these solders play in laser assisted tissue repair.
As noted above, it is known that collagen fibers play an important role in LTW. Welding of the tissue may occur by fusion of the collagen fibers. Unfortunately, collagen cannot be dissolved in water directly. It only can be dissolved in acid, alkali or heavy salt solutions. Because its dissolution may damage the living welded tissue, there is no report of using collagen as a solder for LTW at present.
Gelatin is a collagen-degraded product that is water-soluble. It is an incomplete protein containing only a small number of the essential amino acids. Structurally, gelatin molecules contain repeating sequences of glycine-X-Y triplets, where X and Y are frequently the amino acids proline and hydroxyproline. Their sequences are responsible for the triple helical structure of gelatin and its intrinsic strength.
The physiochemical properties of gelatin may be modified using processes such as myristoylation and silanization. For example, myristoyl gelatin retains its gel structure at temperatures above body temperature without any crosslinking, and can be used as a sealant for Dacron™ vascular prostheses [Sasajima et al, Myristoyl Gelatin as a Sealant for Dacron Vascular Prostheses. Artificial Organs 1997; 21:287–292].
The use of tissue glues in conjunction with lasers or some other form of photoactivating radiation is known. For example, U.S. Pat. No. 5,552,452 discloses an adhesive of a biocompatible peptide in combination with a flavin photosensitizer that forms an adhesive upon photoactivation.
Similarly, U.S. Pat. No. 6,323,037 claims a composition for tissue welding that contains an active compound, which can be a protein or peptide such as albumin, collagen, myoglobin and fibrinogen, a solvent, and an energy converter. Preferred energy sources are lasers such as Nd:YAG lasers, GaAlAs lasers, Argon lasers and CO2 lasers.
U.S. Pat. No. 6,211,335 claims a fluid protein solder in a solvent that can optionally include a dye. The preferred protein to be used in the solder is albumin.
U.S. Pat. No. 6,217,894 claims a compliant tissue sealant that has polymerizable groups that are highly adherent to the surface, e.g. tissue, to which it is applied. The monomers may include hydrophilic regions consisting of proteins such as gelatin, collagen, albumin, ovalbumin, or polyamino acids.
In the past, certain specified lasers have been used in tissue suturing or welding. For example, U.S. Pat. No. 6,221,068 discloses the use of pulsed delivery of radiation, such as from an Nd:YAG laser, in combination with a dye to weld tissue containing proteins, especially collagen.
It would be beneficial to develop a solder for use in conjunction with laser assisted tissue welding that would have enhanced tensile and torque strength. Methods for welding tissue should have minimal adverse effects on surrounding tissue.